Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells

Our plain-English summary of Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells, by S. Tanaka, N. Choe, A. Iwagaki, et al (Experimental Lung Research, 2000).

The study

• Authors: S. Tanaka, N. Choe, A. Iwagaki, D.R. Hemenway, E. Kagan
• Journal: Experimental Lung Research
• Published: 2000;26(4):241-55
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We showed previously that both crocidolite and chrysotile asbestos inhalation induced a persistent macrophage inflammatory response within the pleural space of the rat. We postulated that the stimulus for pleural macrophage recruitment after asbestos exposure was the induction of monocyte chemoattractant protein-1 (MCP-1) synthesis by pleural mesothelial cells. To test this hypothesis, rat pleural mesothelial cells (RPMC) were cultured with or without chrysotile or crocidolite asbestos fibers (8 micrograms/cm2) in the presence (50 ng/mL) or absence of either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). MCP-1 mRNA expression was assessed by RT-PCR in RPMC cultured for 2 to 24 hours, and MCP-1 protein secretion was measured by ELISA in conditioned medium from 24-hour and 48-hour cultures. Crocidolite and chrysotile fibers induced MCP-1 mRNA expression in RPMC which was maximal after 12 hours in the absence of cytokines, but which peaked after 2 hours when RPMC were challenged with asbestos + TNF-alpha or IL-1 beta. Both types of asbestos also significantly increased MCP-1 protein secretion after 24 and 48 hours (P < .0001), an effect that was potentiated by cytokine stimulation. Rats exposed by inhalation to either chrysotile or crocidolite asbestos fibers also had greater amounts of MCP-1 protein in their pleural lavage fluid than did sham-exposed rats. These findings suggest that MCP-1 secretion by RPMC may have a role in the initiation and/or potentiation of asbestos-induced pleural injury.

In plain English

The authors grew pleural mesothelial cells (cells lining the chest cavity) from Fischer-344 rats in the laboratory. They added chrysotile or crocidolite asbestos, or carbonyl iron particles for comparison, with or without the signaling proteins TNF-alpha or IL-1beta. They measured MCP-1, a protein that attracts immune cells called monocytes. Both asbestos types raised MCP-1 gene activity, peaking at 12 hours without the signaling proteins and 2 hours with them. Asbestos raised MCP-1 protein secretion about 5-fold to 10-fold at 24 hours and 13-fold to 28-fold at 48 hours. Carbonyl iron raised gene activity more modestly than asbestos and had no noticeable effect on secretion when added alone. With the signaling proteins, asbestos raised secretion further, though carbonyl iron did not differ notably from asbestos. Separately, male rats (4 per group) breathed chrysotile, crocidolite or filtered air for 2 weeks. Fourteen days after exposure ended, both asbestos groups had significantly more MCP-1 in chest-cavity washing fluid than air-exposed rats. The authors concluded that the findings emphasize the biologic potential of both asbestos types to induce pleural injury. The study did not address the underlying mechanisms.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiment: cell-culture (in vitro) study of rat pleural mesothelial cells, plus an animal inhalation experiment in rats
• Who was studied: Rat parietal pleural mesothelial cells grown in culture from Fischer-344 rats (passage 9), with 3 independent experiments per condition. For the inhalation part: 3 groups of male 43-day-old Fischer-344 rats, 4 rats per inhalation group. Location: Uniformed Services University of the Health Sciences, Bethesda, Maryland, and University of Vermont.
• Exposure: In culture: NIEHS chrysotile or crocidolite asbestos fibers, or carbonyl iron particles as a control, at 8 micrograms per square centimeter, with or without TNF-alpha or IL-1beta (50 ng/mL). Inhalation: whole-body exposure to NIEHS crocidolite, NIEHS chrysotile, or filtered room air (sham) for 6 hours a day, 5 days a week, over 2 weeks. Time-weighted concentrations were crocidolite 10.52 plus or minus 7.32 mg/m3 and chrysotile 7.21 plus or minus 2.33 mg/m3 (mean plus or minus standard error). Rats were killed 14 days after exposure ended.
• Main results:
  • In cultured cells without added cytokines, crocidolite and chrysotile induced MCP-1 mRNA after 6 hours. The effect peaked at 12 hours and returned to baseline by 24 hours. Peak expression was significantly greater after asbestos than after carbonyl iron (P less than .05).
  • Carbonyl iron particles alone produced a similar but more modest pattern of MCP-1 mRNA expression in the cultured cells.
  • When TNF-alpha or IL-1beta was present together with the particles, MCP-1 mRNA expression was induced earlier and peaked at 2 hours. At that time, the effects of crocidolite or chrysotile were significantly greater than those of the cytokine alone (P less than .05).
  • Without cytokines, unexposed cells secreted negligible MCP-1 protein: 27.0 plus or minus 2.1 pg/mL at 24 hours and 53.6 plus or minus 1.5 pg/mL at 48 hours. Chrysotile or crocidolite increased secretion approximately 5-fold to 10-fold at 24 hours and approximately 13-fold to 28-fold at 48 hours.
  • Without added cytokines, carbonyl iron particles had no noticeable effect on MCP-1 protein secretion by the cultured cells during the 48-hour culture period.
  • Cytokines alone stimulated MCP-1 secretion approximately 50-fold to 200-fold, with IL-1beta greater than TNF-alpha. Secretion was significantly different in cultures that also received crocidolite or chrysotile, and the authors described the effects of asbestos and cytokines as synergistic. In cytokine-stimulated cultures there were no notable differences between carbonyl iron and asbestos.
  • MCP-1 was detectable in pleural lavage fluid from both sham-exposed and asbestos-exposed rats. Fourteen days after exposure ended, crocidolite-exposed and chrysotile-exposed rats (4 rats per group) had significantly greater amounts than sham-exposed rats, with chrysotile greater than crocidolite.
• The authors' conclusion: The authors concluded that both crocidolite and chrysotile upregulated MCP-1 gene expression and protein production by cultured rat pleural mesothelial cells, and that the effects were potentiated by IL-1beta and TNF-alpha. They added that MCP-1 secretion into the pleural space was enhanced after inhalation of both types of asbestos. In their view, these findings emphasize the biologic potential of both commercial types of asbestos to induce pleural injury.
• Limitations the authors state:
  • The authors state that the study did not address the mechanisms by which asbestos increased MCP-1 expression and secretion.
  • The authors state that the ideal control group would have inhaled carbonyl iron, the particle used in the cell experiments; a sham-exposed (filtered air) group was used instead.
  • The authors state that they have no obvious explanation for why MCP-1 levels were still elevated 14 days after asbestos exposure ended.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Mesothelial Cells, Crocidolite, Chrysotile, Macrophage, Tumor Necrosis Factor-alpha (TNF-α), Cytokine.

Related studies

• Soluble ICAM-1, MCP-1, and MIP-2 protein secretion by rat pleural mesothelial cells following exposure to amosite asbestos — G.D. Hill, J.B. Mangum, et al. (2003)
• Asbestos exposure upregulates the adhesion of pleural leukocytes to pleural mesothelial cells via VCAM-1 — N. Choe, J. Zhang, et al. (1999)
• Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres — S.P. Faux, C.E. Houghton, et al. (2000)
• Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro — S. Sridharan, A. Taylor-Just, et al. (2021)
• Mesothelial cells activate the plasma kallikrein-kinin system during pleural inflammation — J.F. Varano Della Vergiliana, S. Lansley, et al. (2011)
• Asbestos fibers and interleukin-1 upregulate the formation of reactive nitrogen species in rat pleural mesothelial cells — N. Choe, S. Tanaka, et al. (1998)

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